Our laboratory has demonstrated the existence of inhibitor(s) of cellular proliferation in the cytosol of human ovarian adenocarcinoma cells, and in the ascites fluid of women with disseminated ovarian cancer. These inhibitory substance(s) are able to inhibit 3H-thymidine uptake by phytohemagglutinin (PHA)-stimulated human lymphocytes, and cell growth, in culture, of the murine leukemia L1210. The inhibitor(s) appear to be glycoproteins with molecular weights of 12,000-15,000 daltons. We propose to purify and characterize the physiocochemical and biological properties of the inhibitory factor(s). Purification, using cell-free ascites fluid, will be accomplished by employing ultrafiltration membranes, molecular sieve chromatography (Sephadex G-50, hydroxyapatite), ion-exchange chromatography (carboxymethylcelulose, Dowex), and affinity chromatography (a specific lectin covalently bound to Sephadex G-l0 or Sepharose). The chemical composition (by various biochemical techniques), molecular weight (by sucrose gradients and gel electrophoresis), sulfhydryl group dependency and cation requirements of the purified inhibitor(s) will be determined. The effect of the inhibitor(s) on target cell DNA, RNA and protein synthesis will also be analyzed. In addition, we will examine the ability of the purified inhibitory material to induce fragmentation of target cell DNA (crude inhibitory extracts appear to function in this manner). Long-term goals are to fully elucidate the chemical structure of the inhibitor(s), to determine their specificity of action by employing various cells lines of lymphoid and nonlymphoid origin, to ascertain their effects on the various components of the cell- and humoral-mediated immune system, and to determine if they have any specific antitumor effects, in vivo, on experimental tumors.